Tantalizing findings have emerged from epidemiologic studies to suggest that the prenatal period may influence disease risk in adult life. Birthweight has received particular attention; low birthweight may increase the risk of cardiovascular and neuropsychiatric diseases, high birthweight may increase risk of breast cancer. While intriguing, the existing literature on birthweight and adult health outcomes has not adequately addressed (1) potential confounding by family factors; (2) the importance of other measures of fetal growth; (3) potential biologic mechanisms; (4) the independent effect of maternal characteristics and exposures; (5) the contribution of postnatal growth; and (6) potential mediation by adult risk factors. The Early Determinants of Adult Health (EDAH) Program Project will address these issues using an integrative approach to investigate early determinants of adult health in three research projects: a cardiovascular risk (CVD) Project, a breast cancer risk (BC) Project, and a neuropsychiatric (NP) Project. We will recruit offspring of pregnant women who were enrolled during 1959 to 1967 in two birth cohorts: a New England cohort (Boston and Providence sites of the Collaborative Perinatal Project) and a California cohort (Child Health and Development Study). The offspring are now 35-43 years old--an ideal age to start measuring intermediate markers and following for adult diseases. The centerpiece of the study is a Sibling sample, which will enable us to control for family factors such as socioeconomic status. The Sibling sample is complemented by two Single Child samples which comprise individuals with high birthweight and with exposure to preeclampsia. The total combined sample is 2538 individuals (Sibling sample, 2000 individuals; high birthweight Single Child sample, 350 individuals; and Preeclampsia Single Child sample, 178 individuals). Exposure information will be derived from prospectively collected pre and postnatal data on mothers, infants, and childhood growth, as well as from serologic analysis of archived maternal prenatal sera. We will combine these pre and postnatal data with the adult interview and clinical data in the three health domains. The EDAH is a collaborative research program which cuts across birth cohorts, academic institutions, and scientific domains. Thus, the Program Project will be conducted as partnership of research teams at Columbia and Harvard Universities, with California investigators also playing a leading role. In addition to the CVD, BC, and NP Projects, it includes four Cores: the Administrative and Scientific Leadership (ASL) Core, the Location and Assessment (LA) Core, the Biostatistics and Data Management (BDM) Core, and the Serology/Hormone (S/H) Core. By bringing together expertise across institutions and scientific disciplines, and combining two large birth cohorts to implement a novel design, the study provides an unparalleled opportunity to answer questions about early antecedents of chronic disease.